Dear Readers, over the past two decades, the prevalence of allergies has significantly increased in developed and developing countries. Overall, 20-30% of the world’s population currently suffer from allergies. This increase is of concern since children appear to be particularly affected. According to the World Allergy Organization, one in four European children suffers from an allergy. Allergic diseases are of multifactorial origin and may result from both genetic and environmental factors, thus risk factors and aggravating factors such as pollution or smoking are increasingly characterized and taken into account in preventive treatments.

In this context and knowing that the microbiota is involved in the development of immune responses, what is the role of bacterial communities in the development of allergies? For example, recent epidemiological data from several studies have shown a potential effect of Cesarean sections (i.e. a disruption of early colonization in the newborn) on the development of allergic asthma. To provide some answers in this newsletter, Prof. Roberto Berni Canani (Naples, Italy) and his team have analysed the level of involvement of the gut microbiota in the pathophysiology of allergy. In addition to highlighting dysbiosis in cases of food allergy or atopic dermatitis, recent studies have shown that the decrease in short-chain fatty acids, produced by the microbiota according to the diet may be involved in the development of allergy via the immune system.

In addition to this detailed analysis, international studies showing the presence of Fusobacterium nucleatum in primitive and metastatic tissues of most patients with colorectal cancer, suggesting a role in tumour progression, are discussed. In a second commented article, the adaptation mechanisms of Escherichia coli, a bacterium found in large proportions in children with cystic fibrosis, to a fatrich gut environment are stressed.

The feedback on the highlights of the GUT Summit (March 10-11, Rome, Italy) and of the 25th UEGW Congress (October 28-November 1, 2017, Barcelona, Spain) provides an opportunity to be kept informed of the latest advances in research. This is also the case for the press review, which focuses on the potential promising role of the gut microbiota on the efficacy of anti-cancer treatments with immunotherapy and on the relationship between delivery mode and infant microbiota regarding the intergenerational transmission of excess weight and obesity. Enjoy your reading!

TARGETING THE MICROBIOTA TO COMBAT ALLERGIES

Dysbiotic gut microbiota plays an important role in the development of allergic diseases, in particular food allergies. The gut microbiota drives the maturation and function of thte Immune system, and genetic, environmental, and dietary factors may alter the commensal microbiota, leading to a dysregulation of Immune function. Several factors responsible for dysbiosis have been associated with the occurrence of allergies, such as Caesarean delivery, the lack of breast milk, the use of drugs (mainly been consistently associated with allergies, but evidence suggests that gut dysbiosis occurs even before allergies present. Shortchain fatty acids (SCFAs) are crucial gut microbiota-derived metabolites involved in cross-talk with the immune system. Targeting the composition and function of the gut microbiota represents a promising strategy against allergic diseases, in particular, against childhood food allergies.

THE ROLE OF FUSOBACTERIUM IN COLORECTAL CANCER

Colorectal cancers (CRCs) comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is one of the most prevalent bacterial species in CRC tissues. Here, the authors show that colonisation of human CRC with Fusobacterium and its associated microbiome (including the Bacteroides, Selenomonas and Prevotella species) is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumours. In situ hybridisation analysis revealed that Fusobacterium is mainly associated with cancer cells in metastatic lesions. In mouse xenografts of human primary colorectal adenocarcinomas, Fusobacterium and its associated microbiome remains viable despite successive passages. Treatment of CRC xenografted mice with metronidazole, an antibiotic, reduces Fusobacterium load, cancer cell proliferation, and overall tumour growth. These observations should prompt further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated CRC.

ADAPTATION OF COMMENSAL ESCHERICHIA COLI IN THE INTESTINAL TRACT OF YOUNG CHILDREN WITH CYSTIC FIBROSIS

The mature human gut microbiota is established during the first years of life, and altered intestinal microbiomes have been associated with several human health disorders. Escherichia coli usually represents less than 1% of the human intestinal microbiome, whereas in cystic fibrosis (CF), greater than 50% relative abundance is common and correlates with intestinal inflammation and faecal fat malabsorption. Despite the proliferation of E. coli and other Proteobacteria in conditions involving chronic gastrointestinal tract inflammation, little is known about adaptation of specific characteristics associated with microbiota clonal expansion. This study shows that E. coli isolated from faecal samples of young children with CF has adapted to growth on glycerol, a major component of faecal fat. E. coli isolates from different CF patients demonstrate an increased growth rate in the presence of glycerol compared with E. coli from healthy controls, and unrelated CF E. coli strains have independently acquired this growth trait. Furthermore, CF and control E. coli isolates have differential gene expression when grown in minimal media with glycerol as the sole carbon source. While CF isolates display a growth-promoting transcriptional profile, control isolates engage stress and stationary-phase programmes, which likely results in slower growth rates. These results indicate that there is selection of unique characteristics within the microbiome of individuals with CF, which could contribute to individual disease outcomes.

INTESTINAL MICROBIOTA MODULATES TUMOUR RESPONSE IN CANCER PATIENTS

Over the last 10 years, tremendous advances have been made for cancer patients using new treatment strategies, including immune checkpoint inhibitors that target cytotoxic T-lymphocyte-associated antigen (CTLA-4) and programmed death 1 (PD-1) protein. However, therapeutic responses to these new treatment modalities are often heterogeneous, and some non-responder patients have been reported.

MATERNAL OBESITY DURING PREGNANCY AND DELIVERY MODE

Obesity is a global health problem in children as well as adults, and microbiota composition and alterations in patients with obesity have been evaluated. There is an increasing trend for Caesarean delivery worldwide. Excessive maternal weight or obesity during pregnancy is associated with higher rates of Caesarean delivery, and children delivered by Caesarean section are more likely to develop obesity compared to those delivered vaginally.

Report from the conference

28/10

UEG Week

Barcelona - Spain

The 25th edition of the UEG WEEK was held in Barcelona between October 28 and November 1, 2017.

09/03

GMFH

Rome - Italia

The 7th GMFH summit was held in Rome on March 9-11, 2018. Once again, this year, internationally renowned physicians and researchers met to share the latest scientific advances in the field of microbiota.